Signal transduction in thymus development

Reciprocal interaction between bone marrow derived lymphoid precursor cells and the thymic environment leads, through a series of developmental events , to the generation of a diverse repertoire of functional T-cells. During t hymopoiesis fetal liver or bone marrow derived precursors enter the thymus and develop into mature T-cells in response to cues derived from the enviro nment. The thymic micro-environment provides signals to the lymphoid cells as a result of cell-cell interactions, locally produced cytokines, chemokin es and hormones. Developing thymocytes, in turn, influence the thymic strom a to form a supportive micro-environment. Stage-specific signals provide an exquisite balance between cellular proliferation, differentiation, cell su rvival and death. The result of this intricate signaling concert is the pro duction of the requisite numbers of well educated self-restricted T-cells. Mature T-cells are exported to the peripheral lymphoid organs, where, upon encountering antigen, naive T-cells further mature into effector cells that provide cytolytic or T helper functions. While there are extra-thymic loca tions for T-cell development, majority of T-cells in peripheral lymphoid or gans are thymus derived. In mice and humans, T-cells develop throughout lif e although the efficacy declines significantly with age. It is not clear if this is a direct consequence of deterioration of the thymic environment by involution, a paucity of bone marrow derived precursors, or both. However, new data clearly shows that the involuted adult thymus retains the ability to generate new T-cells. Recent advances have revealed many components of an exquisitely balanced signaling cascades that regulate cell fate, cellula r proliferation and cell death in the thymus. This article describes fundam ental features of developing thymocytes and the thymic micro-environment as they relate to the signaling pathways.